UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Targeting multiple angiogenic pathways for the treatment of neuroblastoma

Williams, RF; Myers, AL; Sims, TL; Ng, CY; Nathwani, AC; Davidoff, AM; (2010) Targeting multiple angiogenic pathways for the treatment of neuroblastoma. JOURNAL OF PEDIATRIC SURGERY , 45 (6) 1103 - 1109. 10.1016/j.jpedsurg.2010.02.073.

Full text not available from this repository.

Abstract

Purpose: Resistance to angiogenesis inhibition can occur through the upregulation of alternative mediators of neovascularization. We used a combination of angiogenesis inhibitors with different mechanisms of action, interferon-beta (IFN-beta) and rapamycin, to target multiple angiogenic pathways to treat neuroblastoma xenografts.Methods: Subcutaneous and retroperitoneal neuroblastoma xenografts (NB-1691 and SK-N-AS) were used. Continuous delivery of IFN-beta was achieved with adeno-associated virus vector-mediated, liver-targeted gene transfer. Rapamycin was delivered intraperitoneally (5 mg/kg per day). After 2 weeks of treatment, tumor size was measured, and tumor vasculature was evaluated with intravital microscopy and immunohistochemistry.Results: Rapamycin and IFN-beta, alone and in combination, had little effect on tumor cell viability in vitro. In vivo, combination therapy led to fewer intratumoral vessels (69% of control), and the remaining vessels had an altered phenotype, being covered with significantly more pericytes (13x control). Final tumor size was significantly less than controls in all tumor models, with combination therapy having a greater antitumor effect than either monotherapy.Conclusion: The combination of IFN-beta and rapamycin altered the vasculature of neuroblastoma xenografts and resulted in significant tumor inhibition. The use of combinations of antiangiogenic agents should be further evaluated for the treatment of neuroblastoma and other solid tumors. (C) 2010 Elsevier Inc. All rights reserved.

Type: Article
Title: Targeting multiple angiogenic pathways for the treatment of neuroblastoma
Location: Washington, DC
DOI: 10.1016/j.jpedsurg.2010.02.073
Keywords: Interferon-beta, Rapamycin, Neuroblastoma, Angiogenesis, TUMOR VASCULATURE, IN-VIVO, GROWTH, INHIBITION, RAPAMYCIN, DELIVERY, MODEL, VINBLASTINE, EXPRESSION, EFFICACY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1330944
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item